Pressure ulcers are a common complication of prone orthopaedic surgery, causing pain and inconvenience to patients. This study aimed to evaluate a comprehensive nursing intervention for pressure ulcer formation in these patients. A total of 120 patients undergoing prone orthopaedic surgery were randomly divided into two groups. The study group (60 patients) received a comprehensive nursing intervention, whereas the control group (60 patients) received a routine nursing intervention. After 2 weeks, the comprehensive nursing intervention significantly reduced the incidence and degree of pressure sores and led to a shorter recovery time than the routine nursing intervention (p < 0.05). The incidence of postoperative wound complications was decreased, and patient satisfaction was significantly improved (p < 0.05). The Hamilton Anxiety Scale, Hamilton Depression Scale and visual analogue scale scores of the study group were significantly lower than those of the control group, and the Short Form 36 Health Survey Questionnaire scores were higher than those of the control group (p < 0.05). A comprehensive nursing intervention can significantly reduce the incidence and degree of pressure ulcers, accelerate recovery time, reduce postoperative wound complications and improve the quality of life and satisfaction of patients undergoing prone orthopaedic surgery.